Negative Pressure Wound Therapy vs Conventional Wound Treatment in Subcutaneous Abdominal Wound Healing Impairment: The SAWHI Randomized Clinical Trial.

Importance: Negative pressure wound therapy (NPWT) is an established treatment option, but there is no evidence of benefit for subcutaneous abdominal wound healing impairment (SAWHI). Objective: To evaluate the effectiveness and safety of NPWT for SAWHI after surgery in clinical practice. Design, Setting, and Participants: The multicenter, multinational, observer-blinded, randomized clinical SAWHI study enrolled patients between August 2, 2011, and January 31, 2018. The last follow-up date was June 11, 2018. The trial included 34 abdominal surgical departments of hospitals in Germany, Belgium, and the Netherlands, and 539 consecutive, compliant adult patients with SAWHI after surgery without fascia dehiscence were randomly assigned to the treatment arms in a 1:1 ratio stratified by study site and wound size using a centralized web-based tool. A total of 507 study participants (NPWT, 256; CWT, 251) were assessed for the primary end point in the modified intention-to-treat (ITT) population. Interventions: Negative pressure wound therapy and conventional wound treatment (CWT). Main Outcomes and Measures: The primary outcome was time until wound closure (delayed primary closure or by secondary intention) within 42 days. Safety analysis comprised the adverse events (AEs). Secondary outcomes included wound closure rate, quality of life (SF-36), pain, and patient satisfaction. Results: Of the 507 study participants included in the modified ITT population, 287 were men (56.6%) (NPWT, 155 [60.5%] and CWT, 132 [52.6%]) and 220 were women (43.4%) (NPWT, 101 [39.5%] and CWT 119 [47.4%]). The median (IQR) age of the participants was 66 (18) years in the NPWT arm and 66 (20) years in the CWT arm. Mean time to wound closure was significantly shorter in the NPWT arm (36.1 days) than in the CWT arm (39.1 days) (difference, 3.0 days; 95% CI 1.6-4.4; P < .001). Wound closure rate within 42 days was significantly higher with NPWT (35.9%) than with CWT (21.5%) (difference, 14.4%; 95% CI, 6.6%-22.2%; P < .001). In the therapy-compliant population, excluding study participants with unauthorized treatment changes (NPWT, 22; CWT, 50), the risk for wound-related AEs was higher in the NPWT arm (risk ratio, 1.51; 95% CI, 0.99-2.35). Conclusions and Relevance: Negative pressure wound therapy is an effective treatment option for SAWHI after surgery; however, it causes more wound-related AEs. Trial Registration: ClinicalTrials.gov Identifier: NCT01528033.

Kinetics of isoflurane and sevoflurane in a unidirectional displacement flow and the relevance to anesthetic gas exposure by operating room personnel.

International guidelines recommend the use of ventilation systems in operating rooms to reduce the concentration of potentially hazardous substances such as anesthetic gases. The exhaust air grilles of these systems are typically located in the lower corners of the operating room and pick up two-thirds of the air volume, whereas the final third is taken from near the ceiling, which guarantees an optimal perfusion of the operating room with a sterile filtered air supply. However, this setup is also employed because anesthetic gases have a higher molecular weight than the components of air and should pool on the floor if movement is kept to a minimum and if a ventilation system with a unidirectional displacement flow is employed. However, this anticipated pooling of volatile anesthetics at the floor level has never been proven. Thus, we herein investigated the flow behaviors of isoflurane, sevoflurane, and carbon dioxide (for comparison) in a measuring chamber sized 2.46 × 1.85 × 5.40 m with a velocity of 0.3 m/sec and a degree of turbulence <20%. Gas concentrations were measured at 1,728 measuring positions throughout the measuring chamber, and the flow behaviors of isoflurane and sevoflurane were found to be similar, with an overlap of 90%. The largest spread of both gases was 55 cm at 5.4 m from the emission source. Interestingly, neither isoflurane nor sevoflurane was detected at floor level, but a continuous cone-like spreading was observed due to gravity. In contrast, carbon dioxide accumulated at floor level in the form of a gas cloud. Thus, floor level exhaust ventilation systems are likely unsuitable for the collection and removal of anesthetic gases from operating rooms.

Importance of Pancreatic Enzyme Replacement Therapy after Surgery of Cancer of the Esophagus or the Esophagogastric Junction.

After surgical treatment of cancer of the esophagus or the esophagogastric junction we observed steatorrhea, which is so far seldom reported. We analyzed all patients treated in our rehabilitation clinic between 2011 and 2014 and focused on the impact of surgery on digestion of fat. Reported steatorrhea was anamnestic, no pancreatic function test was made. Here we show the results from 51 patients. Twenty-three (45%) of the patients reported steatorrhea. Assuming decreased pancreatic function pancreatic enzyme replacement therapy (PERT) was started or modified during the rehabilitation stay (in the following called STEA+). These patients were compared with the patients without steatorrhea and without PERT (STEA-). Maximum weight loss between surgery and rehabilitation start was 18 kg in STEA+ patient and 15.3 kg in STEA- patients. STEA+ patients gained more weight under PERT during the rehabilitation phase (3 wk) than STEA- patients without PERT (+1.0 kg vs. -0.3 kg, P = 0.032). We report for the first time, that patients after cancer related esophageal surgery show anamnestic signs of exocrine pancreas insufficiency and need PERT to gain body weight.

Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial.

BACKGROUND: Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery, and triclosan-coated sutures were developed to reduce their occurrence. The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure, compared with non-coated PDS II sutures, in the prevention of surgical site infections. METHODS: This multicentre, randomised controlled group-sequential superiority trial was done in 24 German hospitals. Adult patients (aged ≥18 years) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion. Exclusion criteria were impaired mental state, language problems, and participation in another intervention trial that interfered with the intervention or outcome of this trial. A central web-based randomisation tool was used to randomly assign eligible participants by permuted block randomisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures (PDS Plus) or uncoated sutures (PDS II) for abdominal fascia closure. The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation. Patients, surgeons, and the outcome assessors were masked to group assignment. Interim and final analyses were by modified intention to treat. This trial is registered with the German Clinical Trials Register, number DRKS00000390. FINDINGS: Between April 7, 2010, and Oct 19, 2012, 1224 patients were randomly assigned to intervention groups (607 to PDS Plus, and 617 to PDS II), of whom 1185 (587 PDS Plus and 598 PDS II) were analysed by intention to treat. The study groups were well balanced in terms of patient and procedure characteristics. The occurrence of surgical site infections did not differ between the PDS Plus group (87 [14·8%] of 587) and the PDS II group (96 [16·1%] of 598; OR 0·91, 95% CI 0·66-1·25; p=0·64). Serious adverse events also did not differ between the groups-146 of 583 (25·0%) patients treated with PDS Plus had at least one serious adverse event, compared with 138 of 602 (22·9%) patients treated with PDS II; p=0·39). INTERPRETATION: Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy. Innovative, multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections. FUNDING: Johnson & Johnson Medical Limited.

HAnd Suture Versus STApling for Closure of Loop Ileostomy (HASTA Trial): results of a multicenter randomized trial (DRKS00000040).

OBJECTIVES: The objective of the HASTA trial was to compare hand suture versus stapling loop ileostomy closure in a randomized controlled trial. BACKGROUND: Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy after low anterior resection. The best surgical technique for closure of loop ileostomy has not been defined yet. METHODS: HASTA trial is a multicenter pragmatic randomized controlled surgical trial with 2 parallel groups to compare hand suture versus stapling for closure of loop ileostomy. The primary endpoint was the rate of bowel obstruction within 30 days after ileostomy closure. RESULTS: A total of 337 randomized patients undergoing closure of loop ileostomy after low anterior resection because of rectal cancer in 27 centers were included. The overall rate of postoperative ileus after ileostomy closure was 13.4%. Seventeen of 165 (10.3%) patients in the stapler group and 27 of 163 (16.6%) in the hand suture group developed bowel obstruction within 30 days postoperatively [odds ratio (OR) = 1.72; 95% confidence interval (CI): 0.89-3.31 = 0.10]. Duration of surgical intervention was significantly shorter in the stapler group (15 minutes; P < 0.001). Multivariable analysis of potential risk factors did not reveal any significant correlation with development of postoperative ileus. Rate of anastomotic leakage (stapler: 3.0%, hand suture: 1.8%, P = 0.48) did not differ significantly as well as all other secondary endpoints. CONCLUSIONS: Hand-sewn anastomosis versus stapler ileo-ileostomy for ileostomy closure are equally effective in terms of postoperative bowel obstruction, with stapler anastomosis leading to a shorter operation time. Postoperative ileus after ileostomy reversal remains a relevant complication.

CD11c-expressing cells reside in the juxtavascular parenchyma and extend processes into the glia limitans of the mouse nervous system.

Recent studies demonstrated that primary immune responses can be induced within the brain depending on vessel-associated cells expressing markers of dendritic cells (DC). Using mice transcribing the green fluorescent protein (GFP) under the promoter of the DC marker CD11c, we determined the distribution, phenotype, and source of CD11c+ cells in non-diseased brains. Predilection areas of multiple sclerosis (MS) lesions (periventricular area, adjacent fibre tracts, and optical nerve) were preferentially populated by CD11c+ cells. Most CD11c+ cells were located within the juxtavascular parenchyma rather than the perivascular spaces. Virtually all CD11c+ cells co-expressed ionized calcium-binding adaptor molecule 1 (IBA-1), CD11b, while detectable levels of major histocompatibility complex II (MHC-II) in non-diseased mice was restricted to CD11c+ cells of the choroid plexus. Cellular processes project into the glia limitans which may allow transport and/or presentation of intraparenchymal antigens to extravasated T cells in perivascular spaces. In chimeric mice bearing CD11c-GFP bone marrow, fluorescent cells appeared in the CNS between 8 and 12 weeks after transplantation. In organotypic slice cultures from CD11c-GFP mice, the number of fluorescent cells strongly increased within 72 h. Strikingly, using anti-CD209, an established marker for human DC, a similar population was detected in human brains. Thus, we show for the first time that CD11c+ cells can not only be recruited from the blood into the parenchyma, but also develop from an intraneural precursor in situ. Dysbalance in their recruitment/development may be an initial step in the pathogenesis of chronic (autoimmune) neuroinflammatory diseases such as MS.

Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation.

The tryptophan (trp)-catabolizing enzyme indolamine 2,3-dioxygenase (IDO) is induced by the T helper 1 (Th 1) cytokine IFN-gamma during infections in various tissues including the brain. Recent studies demonstrated an immune modulatory function of this enzyme, since IDO-mediated depletion of trp hinders T cell proliferation, while its inhibition by 1-methyl-tryptophan (1-Mt) induces breakdown of immune tolerance in the placenta, leading to rejection of allogeneic concepti. Here, we tested IDO expression and function during experimental autoimmune encephalomyelitis (EAE) actively induced in adult SJL mice by immunization with PLP139-151. IDO activity (determined by HPLC analysis of the kynurenine/tryptophan ratio) was increased in the spleen during the preclinical phase, and within the brain and spinal cord at the onset of symptoms. Immunocytochemistry revealed macrophages/activated microglia expressing IDO during EAE and in vitro experiments confirmed IDO induction in microglia upon IFN-gamma treatment with synergistic effects of TNF-alpha. Inhibition of IDO by systemic administration of 1-Mt at clinical onset significantly exacerbated disease scores. From these data, it is tempting to speculate that IFN-gamma from encephalitogenic Th 1 cells induces local IDO expression, thereby initiating a negative feedback loop which may underlie the self-limitation of autoimmune inflammation during EAE and multiple sclerosis.

IDO (indolamine 2,3-dioxygenase) expression and function in the CNS.

From an immunological perspective the placenta is an allograft and therefore requires a special immune suppressive status termed immune privilege. Other organs of the body, which possess poor regenerative capacity share this special status, e.g. the brain, the eye and the gonads. The biological function of immune privilege in all these tissues is to protect them from inflammation-mediated injury. The mechanism maintaining immune privilege are poorly understood and are apparently site-specific. In the placenta, inhibition of IDO leads to spontaneous abortion, showing the crucial role of this enzyme for the maintenance of immune privilege. By catabolizing extracellular tryptophan IDO inhibits local T cell proliferation thereby preventing placental rejection. Here, we show that this mechanism can also be active in suppressing inflammatory responses in the CNS, where inflammations must be tightly regulated to prevent the loss of irreplaceable neurons. Employing RT-PCR and Western blot analysis we could show that, upon activation with the pro-inflammatory cytokine interferon-gamma, astrocytes and microglia are capable of expressing IDO in vitro and in vivo. To test the functional capacity of IDO in the CNS, we performed blockade experiments using actively induced experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease which correlates to the human disease multiple sclerosis (MS). Inhibition of IDO activity by daily subcutaneous administration of the specific IDO inhibitor 1-methyl-DL-tryptophan during EAE significantly exacerbates EAE, shown by comparing clinical disease scores. Thus, local expression of IDO during inflammation is apparently a self-protection mechanism which limits antigen-specific immune responses in the CNS.